Having all but clinched a $46.8 billion deal to acquire the rest of Genentech Inc., Swiss pharmaceutical giant Roche Holding AG faces a potentially bigger challenge: How to integrate and squeeze value out of the pioneering California-based biotech firm without killing it.

Roche executives endured an eight-month struggle to gain full control of Genentech on the firm belief that the combination will generate big rewards, including greater income from Genentech's drugs and a steady flow of new products at a time when many big...